Soluble ST2:A Novel Biomarker for Diagnosis and Prognosis of Cardiovascular Disease

The increasing incidence of cardiovascular disease(CVD)is a significant global health concern,affecting millions of individuals each year.Accurate diagnosis of acute CVD poses a formidable challenge,as misdiagnosis can significantly decrease patient survival rates.Traditional biomarkers have played a vital role in the diagnosis and prognosis of CVDs,but they can be influenced by various factors,such as age,sex,and renal function.Soluble ST2(sST2)is a novel biomarker that is closely associated with different CVDs.Its low reference change value makes it suitable for continuous measurement,unaffected by age,kidney function,and other confounding factors,facilitating risk stratification of CVDs.Furthermore,the combination of sST2 with other biomarkers can enhance diagnostic accuracy and prognostic value.This review aims to provide a comprehensive overview of sST2,focusing on its diagnostic and prognostic value as a myocardial marker for different types of CVDs and discussing the current limitations of sST2.

Establishment of an optimized CTC detection model consisting of EpCAM,MUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics

Objective:Emerging studies have demonstrated the promising clinical value of circulating tumor cells(CTCs)for diagnosis,disease assessment,treatment monitoring and prognosis in epithelial ovarian cancer.However,the clinical application of CTC remains restricted due to diverse detection techniques with variable sensitivity and specificity and a lack of common standards.Methods:We enrolled 160 patients with epithelial ovarian cancer as the experimental group,and 90 patients including 50 patients with benign ovarian tumor and 40 healthy females as the control group.We enriched CTCs with immunomagnetic beads targeting two epithelial cell surface antigens(EpCAM and MUC1),and used multiple reverse transcription-polymerase chain reaction(RT-PCR)detecting three markers(EpCAM,MUC1 and WT1)for quantification.And then we used a binary logistic regression analysis and focused on EpCAM,MUC1 and WT1 to establish an optimized CTC detection model.Results:The sensitivity and specificity of the optimized model is 79.4%and 92.2%,respectively.The specificity of the CTC detection model is significantly higher than CA125(92.2%vs.82.2%,P=0.044),and the detection rate of CTCs was higher than the positive rate of CA125(74.5%vs.58.2%,P=0.069)in early-stage patients(stage I and II).The detection rate of CTCs was significantly higher in patients with ascitic volume≥500 mL,suboptimal cytoreductive surgery and elevated serum CA125 level after 2 courses of chemotherapy(P<0.05).The detection rate of CTC;and CTC;was significantly higher in chemo-resistant patients(26.3%vs.11.9%;26.4%vs.13.4%,P<0.05).The median progression-free survival time for CTC;patients trended to be longer than CTC;patients,and overall survival was shorter in CTC;patients(P=0.043).Conclusions:Our study presents an optimized detection model for CTCs,which consists of the expression levels of three markers(EpCAM,MUC1 and WT1).In comparison with CA125,our model has high specificity and demonstrates better diagnostic values,especially for early-stage ovarian cancer.Detection of CTC;and CTC;had predictive value for chemotherapy resistance,and the detection of CTC;suggested poor prognosis.

Upgrading the definition of early gastric cancer: better staging means more appropriate treatment

Since Murakami defined early gastric cancer(EGC) as a "carcinoma limited to the gastric mucosa and/or submucosa regardless of the lymph node status", several authors have focused on the most influential histopathological parameters for predicting the development of lymph node metastases by considering the lymph node status as an important prognostic factor. A few authors have also considered the depth of invasion as one of the keys to explaining the existence of subgroups of patients affected by EGC with poor prognoses. In any case, EGC is still considered an initial phase of tumor progression with good prognosis. The introduction of modern endoscopic devices has allowed a precise diagnosis of early lesions, which can lead to improved definitions of tumors that can be radically treated with endoscopic mucosal resection or endoscopic submucosal dissection(ESD). Given the widespread use of these techniques, the Japanese Gastric Cancer Association( JGCA) identified in 2011 the standard criteria that should exclude the presence of lymph node metastases. At that time, EGCs with nodal involvement should have been asserted as no longer fitting the definition of an early tumor. Some authors have also demonstrated that the morphological growth pattern of a tumor, according to Kodama's classification, is one of the most important prognostic factors, thereby suggesting the need to report it in histopathological drafts. Notwithstanding the acquired knowledge regarding the clinical behavior of EGC, Murakami's definition is still being used. This definition needs to be upgraded according to the modern staging of the disease so that the appropriate treatment would be selected.

Aberrant methylation of SPARC in human hepatocellular carcinoma and its clinical implication

AIM:To investigate the methylation status of secreted protein acidic and rich in cysteine(SPARC) in human hepatocellular carcinoma(HCC) and evaluate its clinical implication.METHODS:The methylation status of SPARC was analyzed in one HCC cell line(SMMC-7721) and 60 pairs of HCC and corresponding nontumorous tissues by methylation-specific polymerase chain reaction and bisulfite sequencing.The expression of SPARC mRNA and protein were examined by reverse transcription polymerase chain reaction and immunohistochemistry,respectively.The correlations between the methylation status and the gene expression,the clinicopathological parameters,as well as the prognosis after surgery were analyzed.RESULTS:In the SMMC-7721 cell line,the loss of SPARC expression was correlated with the aberrant methylation and could be reactivated by the demethylating agent 5-aza-2'-deoxycytidine.Methylation frequency of SPARC in HCC was significantly higher than that in the corresponding nontumorous tissues(45/60 vs 7/60,P < 0.001),and it was correlated with the pathological classification(P = 0.019).The downregulation of the SPARC mRNA expression in HCC was correlated with the SPARC methylation(P = 0.040).The patients with methylated SPARC had a poorer overall survival than those without methylated SPARC(28.0 mo vs 41.0 mo,P = 0.043).CONCLUSION:Aberrant methylation is an important mechanism for SPARC inactivation in HCC and SPARC methylation may be a promising biomarker for the diagnosis and prognosis of HCC.

STAPHYLOCOCCAL SCALDED SKIN SYNDROME: RETROSPECTIVE ANALYSIS OF 82 CASES

Objective To explore distinctive clinical manifestations and appropriate treatment, and assess prognosis of staphylococcal scalded skin syndrome （SSSS）. Methods A retrospective analysis was conducted of the data of 82 cases of SSSS hospitalized at Xinhua Hospital during the period from May 1993 to September 2003. Results The disease in all the 82 patients occurred in their first decade （mean 2.5 years）. Possible predisposing factors were found in 48 （58. 5% ）. Fever was present in 78 （95. 1% ）. Radial spokes of crusting around mouth were present in 80 （ 97. 6% ）. Erythema began on the face, especially around the mouth and eye in 63 （ 76. 8% ）. The course was acute in all cases and the eruptions quickly spread to the whole body within one day to two days. Of the 82 cases of SSSS, 47 were complete form of SSSS, 27 were abortive form of SSSS, and 8 were between the two forms. Staphylococcus aureus with positive staphylocoagulase was isolated from the possible primary infection sites including pharynx, eyelid, conjunctiva, nose, ear, and skin in 18 of 31 patients. Microbiological cultures of bullae and little pustulae developed after the onset were negative in 16 cases. All the 82 patients completely recovered after receiving antibiotic therapy （ ceftriaxone, oxacillin） alone or in combination with human immunoglobulin （IVIG） therapy. Additional IVIG therapy was used in those patients who had systemic involvements such as pneumonia, fever higher than 38. 5℃ or leukocytosis. Conclusion SSSS is a spectrum disease. Besides abortive and complete forms, presenting between the two forms a new form might be appeared in 8 cases who developed both scarlatiniform rash and flaccid bullae. The abortive form and complete form are usually misdiagnosed clinically. Radial spokes of crusting around mouth seem to be characteristic manifestation of SSSS. All the patients in this study had favorable prognosis after receiving prompt diagnosis and appropriate treatment.

Diagnosis,treatment and prognosis of thymoma:an analysis of 116 cases

Objective To study the diagnosis and treatment of thymoma and to assess its prognostic factors.Methods The clinical data of 116 patients with thymoma were collected. A retrospective analysis was performed,by comparing the survival rate calculated by the Kaplan-Meier method with the rate of recurrence or metastasis.Results The standard posteroanterior and lateral chest radiographs were reliable means of detection of most thymomas. Myasthenia gravis was the most commonly paraneoplastic disease (25.0%,29/116). The extensive radical resection was beneficial for reducing the rate of recurrence of stage Ⅰ or stage Ⅱ thymomas (χ 2=4.941,P =0.0219). The survival time could be prolonged by postoperative radiotherapy and chemotherapy. There was a strong correlation between the clinical stage and the histological classification (according to MH classification),through which the invasive behavior of thymoma could be predicted (χ 2=19.76,P =0.007,RR=1.47). The 3- 5- and 10-year survival rates were 81.2%,67.9%,and 40.5%,respectively. Statistical analysis showed a significant negative correlation between the stage and the survival rate (χ 2=29.73,P =0.0000,RR=0.15). Conclusion The prognosis of thymoma depends mainly on the histological classification,clinical stage and multimodality treatment rather than on the paraneoplastic diseases.

Soluble triggering receptor expressed on myeloid cell-1 （sTREM- 1）： a potential biomarker for the diagnosis of infectious diseases

Sensitive and useful biomarkers for the diagnosis and prognosis of infectious diseases have been widely developed. An example of these biomarkers is triggering receptor expressed on myeloid cell-1 （TREM-1）, which is a cell surface receptor expressed on monocytes/macrophages and neutrophils. TREM-1 amplifies inflammation by activating the TREM-1/DAP12 pathway. This pathway is triggered by the interaction of TREM-1 with ligands or stimulation by bacterial lipopolysaccharide. Consequently, pro-inflammatory cytokines and chemokines are secreted. Soluble TREM-1 （sTREM-1） is a special form of TREM-1 that can be directly tested in human body fluids and well-known biomarker for infectious diseases, sTREM-1 level can be potentially used for the early diagnosis and prognosis prediction of some infectious diseases, including infectious pleural effusion, lung infections, sepsis, bacterial meningitis, viral infections （e.g., Crimean Congo hemorrhagic fever and dengue fever）, fungal infections （e.g., Aspergillus infection）, and burn-related infections, sTREM-1 is a more sensitive and specific biomarker than traditional indices, such as C-reactive protein and procalcitonin levels, for these infectious diseases. Therefore, sTREM-1 is a feasible biomarker for the targeted therapy and rapid and early diagnosis of infectious diseases.

Blood Biomarkers in Minor Stroke and Transient Ischemic Attack

Minor stroke and transient ischemic attack（TIA）are common disorders with a high rate of subsequent disabling stroke, so the early recognition and management of minor stroke and TIA is of great importance. At the moment, the diagnosis of these disorders is based on neurologic deficits in a stroke-clinician＇s examination of the patient, supplemented by the results of acute brain imaging.However, high variability in TIA diagnosis has been reported between physicians, even trained vascular neurologists, and image-based diagnostic confirmation is not always readily available. Some patients still have ischemic events despite sustained standard secondary preventive therapy. Blood biomarkers are promising to aid in the diagnosis, risk stratification, and individual treatment of minor stroke and TIA. Some studies are being conducted in this field. This mini-review aims to highlight potential biomarkers for diagnosis and those helpful in predicting the risk of future stroke and the selection of treatment.

Edge biomarkers for classification and prediction of phenotypes

In general,a disease manifests not from malfunction of individual molecules but from failure of the relevant system or network,which can be considered as a set of interactions or edges among molecules.Thus,instead of individual molecules,networks or edges are stable forms to reliably characterize complex diseases.This paper reviews both traditional node biomarkers and edge biomarkers,which have been newly proposed.These biomarkers are classified in terms of their contained information.In particular,we show that edge and network biomarkers provide novel ways of stably and reliably diagnosing the disease state of a sample.First,we categorize the biomarkers based on the information used in the learning and prediction steps.We then briefly introduce conventional node biomarkers,or molecular biomarkers without network information,and their computational approaches.The main focus of this paper is edge and network biomarkers,which exploit network information to improve the accuracy of diagnosis and prognosis.Moreover,by extracting both network and dynamic information from the data,we can develop dynamical network and edge biomarkers.These biomarkers not only diagnose the immediate pre-disease state but also detect the critical molecules or networks by which the biological system progresses from the healthy to the disease state.The identified critical molecules can be used as drug targets,and the critical state indicates the critical point of disease control.The paper also discusses representative biomarker-based methods.

Heel pain： A systematic review

Heel pain is a very common foot disease. Varieties of names such as plantar fasciitis, jogger＇s heel, tennis heal, policeman＇s heel are used to describe it. Mechanical factors are the most common etiology of heel pain. Common causes of hell pain includes： Plantar Fasciitis, Heel Spur, Sever＇s Disease, Heel bump, Achilles Tendinopathy, Heel neuritis, Heel bursitis. The diagnosis is mostly based on clinical examination. Normally, the location of the pain and the absence of associated symptoms indicating a systemic disease strongly suggest the diagnosis. Several therapies exist including rest, physical therapy, stretching, and change in footwear, arch supports, orthotics, night splints, anti-inflammatory agents, and surgery. Almost all patients respond to conservative nonsurgical therapy. Surgery is the last treatment option if all other treatments had failed. Rest, ice, massage, the use of correct exercise and complying with a doctor＇s advice all play important part in helping to recover from this hell pain condition, but getting good quality, suitable shoes with the appropriate amount of support for the whole foot is the most important.

Quantitative Secretome Analysis Reveals Clinical Values of Carbonic Anhydrase Ⅱ in Hepatocellular Carcinoma

Early detection and intervention are key strategies to reduce mortality,increase longterm survival,and improve the therapeutic effects of hepatocellular carcinoma(HCC)patients.Herein,the isobaric tag for relative and absolute quantitation(iTRAQ)-based quantitative proteomic strategy was used to study the secretomes in conditioned media from HCC cancerous tissues,surrounding noncancerous tissues,and distal noncancerous tissues to identify diagnostic and prognostic biomarkers for HCC.In total,22 and 49 dysregulated secretory proteins were identified in the cancerous and surrounding noncancerous tissues,respectively,compared with the distal noncancerous tissues.Among these proteins,carbonic anhydrase II(CA2)was identified to be significantly upregulated in the secretome of cancerous tissues;correspondingly,the serum concentrations of CA2 were remarkably increased in HCC patients compared with that in normal populations.Interestingly,a significant increase of serum CA2 in recurrent HCC patients after radical resection was also confirmed compared with HCC patients without recurrence,and the serum level of CA2 could act as an independent prognostic factor for time to recurrence and overall survival.Regarding the mechanism,the secreted CA2 enhances the migration and invasion of HCC cells by activating the epithelial mesenchymal transition pathway.Taken together,this study identified a novel biomarker for HCC diagnosis and prognosis,and provided a valuable resource of HCC secretome for investigating serological biomarkers.

SCADA data based condition monitoring of wind turbines

Wind turbines（WTs） are quite expensive pieces of equipment in power industry. Maintenance and repair is a critical activity which also consumes lots of time and effort, hence making it a costly affair. Carefully planning the maintenance based upon condition of the equipment would make the process reasonable. Mostly the WTs are equipped with some kind of condition monitoring device/system, which provides the information about the device to the central data base i.e., supervisory control and data acquisition（SCADA） data base. These devices/systems make use of data processing techniques/methods in order to detect and predict faults. The information provided by condition monitoring equipments keeps on recoding in the SCADA data base. This paper dwells upon the techniques/methods/algorithms developed, to carry out diagnosis and prognosis of the faults, based upon SCADA data.Subsequently data driven approaching for SCADA data interpretation has been reviewed and an artificial intelligence（AI） based framework for fault diagnosis and prognosis of WTs using SCADA data is proposed.

Identification of NR3C2 as a functional diagnostic and prognostic biomarker and potential therapeutic target in non‐small cell lung cancer

Background:Non‐small cell lung cancer(NSCLC),including the lung squamous cell carcinoma(LUSC)and lung adenocarcinoma(LUAD)subtypes,is a malignant tumor type with a poor 5‐year survival rate.The identification of new powerful diagnostic biomarkers,prognostic biomarkers,and potential therapeutic targets in NSCLC is urgently required.Methods:The UCSC Xena,UALCAN,and GEO databases were used to screen and analyze differentially expressed genes,regulatory modes,and genetic/epigenetic alterations in NSCLC.The UCSC Xena database,GEO database,tissue microarray,and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values.Gain‐of‐function assays were performed to examine the roles.The ESTIMATE,TIMER,Linked Omics,STRING,and DAVID algorithms were used to analyze potential molecular mechanisms.Results:NR3C2 was identified as a potentially important molecule in NSCLC.NR3C2 is expressed at low levels in NSCLC,LUAD,and LUSC tissues,which is significantly related to the clinical indexes of these patients.Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC,LUAD,and especially LUSC patients.Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients.These results have been confirmed both with database analysis and real‐world clinical samples on a tissue microarray.Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD,while promoter DNA methylation is involved in its downregulation in LUSC.Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential.NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration.NR3C2 co‐expressed genes are involved in many cancer‐related signaling pathways,further supporting a potentially significant role of NR3C2 in NSCLC.Conclusions:NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.